1. Field of the Invention
The present invention relates to methods of treating male erectile dysfunction. The present invention further relates to pharmaceutical compositions useful for treating male erectile dysfunction.
2. Discussion of the Background
Impotence, or lack of a man""s ability to have sexual intercourse, is often the subject of jokes. However, millions of men suffer from this condition. Impotence is generally characterized by an inability to maintain a penile erection, and is often referred to as erectile dysfunction. Erectile dysfunction affects men, regardless of age, place of birth, or prior sexual experience.
In the context of the present invention, the term xe2x80x9cerectile dysfunctionxe2x80x9d refers to certain disorders of the cavernous tissue of the penis and the associated fascia which produce impotence, the inability to attain a sexually functional erection. Impotence is estimated to affect about 10 million men in the United States alone. Impotence results from disruption of any of numerous physiological or psychological factors which cause the blood flow to and from the penis to remain in balance thereby preventing retention of sufficient blood to cause rigid dilation of the corpus cavernosa and spongiosa. In the context of the present invention, the term xe2x80x9cimpotencexe2x80x9d is used in its broadest sense as the inability to attain a sexually functional erection when desired.
Treatments for impotence include psychosexual therapy, hormonal therapy, administration of vasodilators such as nitroglycerin and xcex1-adrenergic blocking agents (hereafter xe2x80x9cxcex1-blockersxe2x80x9d), vascular surgery, implanted penile prostheses, vacuum devices and external aids such as penile splints to support the penis or penile constricting rings to alter the flow of blood through the penis, (see Robert J. Krause, et al. N. Eng. J. Med., vol. 321, No 24, Dec. 14, 1989). Many patients treat their impotence by self injection of vasoactive drugs directly into the corpora cavernosa (see: Forward 1st Symposium International Sur L""Erection Pharmacologique, Nov. 17-19, 1989, Paris, p. 2; Virag, et al., Angiology, vol. 35, pp. 79-87, (1984); and U.S. Pat. Nos. 4,127,118, 4,766,889, and 4,857,059, which are incorporated herein by reference). The drugs most commonly used include xcex1-blockers, such as phenoxybenzamine and phentolamine; smooth muscle relaxants such as papaverine; prostaglandins having a vasoactive function such as prostaglandin E1 and combinations of such drugs having different receptor effects to enhance therapy. Intracavernous injection doses of papaverine are typically in the range of about 7.5 to 160 mg, while doses of phentolamine are in the range of about 0.1 to 10 mg and doses of prostaglandin E1 are in the range of about 2.5 to 50 micrograms (see for example, Kurkle, et al., Urol. Clin. of America, vol. 15, No. 4, pp. 625-629 (1988) and N. Ishii et al., J. of Urol., vol. 141, pp. 323-325 (1989). Vasoactive intestinal peptides have also been reported as producing erection upon intracavernous injection at doses of 10-100 xcexcg (see H. Handelsman, Diagnosis and Treatment of Impotence, U.S. Dept. of Health Services, Agency for Health Care Policy and Research, April 1990).
However, patients often find the injections of vasoactive drugs psychologically disturbing, painful, traumatic, or inconvenient as evidenced by a high discontinuance rate (see S. Althouf, et al., Journal of Sex and Marital Therapy, vol. 15, No. 2, pp. 121-129 (1989). In addition, adverse side effects including priapism, corporeal nodules and diffuse fibrosis, drug tolerance, bruising and hematomas, swelling and ulceration of the penile skin at the injection site have also been reported.
U.S. Pat. No. 4,801,587 and EPA 0357581 disclose the administration of vasodilators via the male urethra to produce erections. The transurethral administration of testosterone has also been reported (see S. M. Milco, Bulletins et Memoirs de la Societa Roumaine D""Endocrinologie, Vol. 5, pp. 434-437 (1989)). It has also been suggested that cocaine administered transurethrally could contribute to an erection (JAMA, vol. 259, No. 21, page 3176 (1988)). A nitroglycerin coated, erection inducing condom is disclosed in U.S. Pat. No. 4,829,991.
However, to date there is no completely effective treatment for male erectile dysfunction. Thus, there remains a need for a method of treating male erectile dysfunction. There also remains a need for compositions which are effective for treating male erectile dysfunction. In particular, there remains a need for methods and compositions for treating impotence which are characterized by a reduced tendency to cause pain, priapism, corporeal nodules, diffuse fibrosis, and scarring.
Accordingly, it is one object of the present invention to provide novel methods for treating male erectile dysfunction.
It is another object of the present invention to provide methods for treating male erectile dysfunction involving topical, meatal, and/or transurethral administration of a pharmaceutical composition.
It is another object of the present invention to provide methods for treating male erectile dysfunction which exhibit a reduced tendency to cause pain or a burning sensation.
It is another object of the present invention to provide methods for treating male erectile dysfunction which exhibit a reduced tendency to cause priapism.
It is another object of the present invention to provide methods for treating male erectile dysfunction which exhibit a reduced tendency to cause corporeal nodules.
It is another object of the present invention to provide methods for treating male erectile dysfunction which exhibit a reduced tendency to cause diffuse fibrosis.
It is another object of the present invention to provide methods for treating male erectile dysfunction which exhibit a reduced tendency to cause scarring of the corpora spongiosum and cavernosa.
It is another object of the present invention to provide novel pharmaceutical compositions which are useful for treating male erectile dysfunction.
It is another object of the present invention to provide pharmaceutical compositions for treating male erectile dysfunction which exhibit a reduced tendency to cause pain or a burning sensation.
It is another object of the present invention to provide pharmaceutical compositions for treating male erectile dysfunction which exhibit a reduced tendency to cause priapism.
It is another object of the present invention to provide pharmaceutical compositions for treating male erectile dysfunction which exhibit a reduced tendency to cause corporeal nodules.
It is another object of the present invention to provide pharmaceutical compositions for treating male erectile dysfunction which are effective when applied topically, meatally, and/or transurethrally.
It is another object of the present invention to provide pharmaceutical compositions for treating male erectile dysfunction which exhibit a reduced tendency to cause diffuse fibrosis.
It is another object of the present invention to provide pharmaceutical compositions for treating male erectile dysfunction which exhibit a reduced tendency to cause scarring of the corpora spongiosum and cavernosa.
These and other objects, which will become clear in the course of the following detailed description, have been achieved by the inventor""s discovery that pharmaceutical compositions, which are in the form of a urethral suppository, and which comprise:
(a) a prostaglandin vasodilator;
(b) a 15-hydroxyprostaglandindehydrogenase inhibitor; and
(c) a base material that is solid at room temperature and releases components (a) and (b) when inserted in the urethra,
are particularly effective for the treatment of male erectile dysfunction even at low doses.
In a preferred embodiment, component (c) is a base material that is solid at room temperature but melts or dissolves when inserted in the urethra to release components (a) and (b).